A Novel Regulated Nanohydrogel Delivery System for Targeted Inner Ear Application
一种用于靶向内耳应用的新型调节纳米水凝胶输送系统
基本信息
- 批准号:8860787
- 负责人:
- 金额:$ 40万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-03-01 至 2020-02-28
- 项目状态:已结题
- 来源:
- 关键词:AffectAnatomyAntibodiesBiocompatibleBiocompatible MaterialsCaliberCellsCellular StructuresChemistryChitosanDevelopmentDiseaseDrug Delivery SystemsDrug FormulationsDrug or chemical Tissue DistributionEarEffectivenessEnzymesEtiologyExposure toFunctional disorderGlycerophosphatesHearingHourHumanHydrogelsImmune systemIn VitroLabelLabyrinthLengthLigandsLigationMAPK8 geneMeasuresMedicalMembraneMethodsModalityModelingMolecularMusNoisePharmaceutical PreparationsPopulationPreventionPropertyRegulationResearch PersonnelRiskSafetyScientistSensorineural Hearing LossSensorySiteSpecificitySteroidsSystemTestingTherapeuticTherapeutic AgentsTimeToxic effectbasechitosanasecontrolled releaseeffective therapyimprovedin vivoinhibitor/antagonistinner ear diseasesinnovationinterestlocal drug deliverymouse modelnanoformulationnanoparticlenovelparticlepreventprotein expressionpublic health relevanceresearch studyround windowtargeted treatment
项目摘要
DESCRIPTION (provided by applicant): Sensorineural Hearing loss (SNHL) is one of the most common sensory deficits in humans, affecting millions of people worldwide, and is primarily attributed to inner ear dysfunction. Although a lot of progress has been made recently in understanding the etiology and molecular mechanisms of this disease, there are almost no non-invasive therapeutic approaches targeting to the pathological sites of the inner ear that are responsible for the majority of SNHL. A targeted multifunctional nanoparticle (MFNP) system (called nanohydrogel) proposed in this study is, to our knowledge, the first system to serve as a platform for the non-invasive delivery of biomaterials into specific inner ear structures for the treatment of the inner ear diseases. The MFNPs are usually smaller than 200 nm in diameter, and can be equipped with several functions, such as the ability to target specific cells, evade the
immune system, and deliver the payload across different barriers. Unfortunately, current nanoparticle delivery systems are unable to efficiently deliver biomaterials to the to specific inner ear structures. These issues can be solved through the use of a biocompatible and biodegradable chitosan-glycerophosphate (CGP) hydrogel, which the principle investigator (PI) has shown to be capable of attaching to the round window membrane (RWM) and efficiently releasing therapeutic agents across the intact membrane in a controlled and sustained manner, and can be regulated using a glycolytic enzyme called chitosanase. Additionally, using innovative "click"-chemistry, MFNPs can incorporate targeting ligands to allow for better selectivity or targeting of these particles to cells of interest. In this proposal, the PI hypotheizes that the use of a regulated CGP-hydrogel-MNFP system (nanohydrogel) would result in a controlled, targeted, and highly effective delivery platform, bringing therapeutic biomaterial agents to specific cellular structures within the inner ear for the treatment of inner ear diseases This unique system has the potential to select ligands or therapeutic biomaterials depending on the need for different therapeutic approaches. The hypothesis is evaluated using a mouse model with different nanohydrogel formulations on the RWM to slowly and steadily release the MFNP into the inner ear. The ability to target specific inner ear cells will be evaluated by measuring the distribution of MFNPs in inner ear structures. To test the effectiveness and safety of this delivery system, the nanohydrogel system will be used to deliver MFNPs to the inner ear for the prevention of noise-induced SNHL in a mouse model. If the use of this novel nanohydrogel system proves to be an effective method of drug delivery for prevention of SNHL, it would signify a major step forward in the non-invasive treatment of inner ear diseases, which are currently untreatable. Moreover, this modular nanohydrogel system would allow for the development of better targeted therapies, extending it to a large variety of targeting moieties and treatment options, for this important functional region that has been marked by limited anatomic access. If this innovative system proves effective and safe, it will represent a major breakthrough in the treatment of the inner ear diseases, where a non-invasive delivery system carrying biomaterials or molecular agents is desperately needed.
描述(申请人提供):感音神经性听力损失(SNHL)是人类最常见的感觉障碍之一,影响全球数百万人,主要归因于内耳功能障碍。虽然最近在了解该病的病因和分子机制方面取得了很大进展,但几乎没有针对内耳病变部位的非侵入性治疗方法,这些部位是SNHL的主要原因。据我们所知,本研究提出的靶向多功能纳米粒子(MFNP)系统(称为纳米水凝胶)是第一个将生物材料非侵入性地输送到特定内耳结构中用于治疗内耳疾病的系统。MFNPs的直径通常小于200纳米,并可以配备几种功能,例如靶向特定细胞的能力,躲避
免疫系统,并提供有效载荷跨越不同的障碍。不幸的是,目前的纳米颗粒输送系统不能有效地将生物材料输送到特定的内耳结构。这些问题可以通过使用生物相容和可生物降解的壳聚糖-甘油磷酸(CGP)水凝胶来解决,首席研究员(PI)已经证明,这种水凝胶能够附着在圆形窗膜(RWM)上,并以受控和持续的方式有效地在完整的膜上释放治疗剂,并且可以使用一种称为壳聚糖酶的糖酵解酶来调节。此外,利用创新的“点击”化学,MFNPs可以结合靶向配体,以允许这些粒子更好地选择性或靶向感兴趣的细胞。在这项建议中,PI假设使用受调控的CGP-水凝胶-MNFP系统(纳米水凝胶)将产生一个受控的、定向的和高效的输送平台,将治疗性生物材料制剂带到内耳内的特定细胞结构中用于治疗内耳疾病。这个独特的系统具有根据不同治疗方法的需要选择配体或治疗性生物材料的潜力。这一假说是通过在RWM上使用不同纳米水凝胶配方的小鼠模型进行评估的,以缓慢而稳定地将MFNP释放到内耳。靶向特定内耳细胞的能力将通过测量MFNPs在内耳结构中的分布来评估。为了测试这种输送系统的有效性和安全性,将使用纳米水凝胶系统将MFNPs输送到内耳,以防止噪声诱导的SNHL在小鼠模型中。如果这种新型纳米水凝胶系统的使用被证明是预防SNHL的一种有效的药物输送方法,它将标志着在非侵入性治疗目前无法治疗的内耳疾病方面向前迈出了重要的一步。此外,这种模块化的纳米水凝胶系统将允许开发更好的靶向疗法,将其扩展到各种靶向部分和治疗选择,用于这一重要的功能区域,其特点是解剖途径有限。如果这一创新系统被证明是有效和安全的,它将代表着内耳疾病治疗方面的重大突破,在内耳疾病的治疗中,迫切需要一种携带生物材料或分子制剂的非侵入性给药系统。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Daqing Li其他文献
Daqing Li的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Daqing Li', 18)}}的其他基金
A novel nanodialysis platform for inner ear detoxification
一种用于内耳排毒的新型纳米透析平台
- 批准号:
10216213 - 财政年份:2019
- 资助金额:
$ 40万 - 项目类别:
A novel nanodialysis platform for inner ear detoxification
一种用于内耳排毒的新型纳米透析平台
- 批准号:
10675694 - 财政年份:2019
- 资助金额:
$ 40万 - 项目类别:
A novel nanodialysis platform for inner ear detoxification
一种用于内耳排毒的新型纳米透析平台
- 批准号:
10440322 - 财政年份:2019
- 资助金额:
$ 40万 - 项目类别:
A Novel Regulated Nanohydrogel Delivery System for Targeted Inner Ear Application
一种用于靶向内耳应用的新型调节纳米水凝胶输送系统
- 批准号:
9017993 - 财政年份:2015
- 资助金额:
$ 40万 - 项目类别:
相似海外基金
Linking Epidermis and Mesophyll Signalling. Anatomy and Impact in Photosynthesis.
连接表皮和叶肉信号传导。
- 批准号:
EP/Z000882/1 - 财政年份:2024
- 资助金额:
$ 40万 - 项目类别:
Fellowship
Digging Deeper with AI: Canada-UK-US Partnership for Next-generation Plant Root Anatomy Segmentation
利用人工智能进行更深入的挖掘:加拿大、英国、美国合作开发下一代植物根部解剖分割
- 批准号:
BB/Y513908/1 - 财政年份:2024
- 资助金额:
$ 40万 - 项目类别:
Research Grant
Doctoral Dissertation Research: Social and ecological influences on brain anatomy
博士论文研究:社会和生态对大脑解剖学的影响
- 批准号:
2235348 - 财政年份:2023
- 资助金额:
$ 40万 - 项目类别:
Standard Grant
Simultaneous development of direct-view and video laryngoscopes based on the anatomy and physiology of the newborn
根据新生儿解剖生理同步开发直视喉镜和视频喉镜
- 批准号:
23K11917 - 财政年份:2023
- 资助金额:
$ 40万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Computational comparative anatomy: Translating between species in neuroscience
计算比较解剖学:神经科学中物种之间的翻译
- 批准号:
BB/X013227/1 - 财政年份:2023
- 资助金额:
$ 40万 - 项目类别:
Research Grant
computational models and analysis of the retinal anatomy and potentially physiology
视网膜解剖学和潜在生理学的计算模型和分析
- 批准号:
2825967 - 财政年份:2023
- 资助金额:
$ 40万 - 项目类别:
Studentship
Genetics of Extreme Phenotypes of OSA and Associated Upper Airway Anatomy
OSA 极端表型的遗传学及相关上呼吸道解剖学
- 批准号:
10555809 - 财政年份:2023
- 资助金额:
$ 40万 - 项目类别:
Development of a novel visualization, labeling, communication and tracking engine for human anatomy.
开发一种新颖的人体解剖学可视化、标签、通信和跟踪引擎。
- 批准号:
10761060 - 财政年份:2023
- 资助金额:
$ 40万 - 项目类别:
Understanding the functional anatomy of nociceptive spinal output neurons
了解伤害性脊髓输出神经元的功能解剖结构
- 批准号:
10751126 - 财政年份:2023
- 资助金额:
$ 40万 - 项目类别:
The Anatomy of Online Reviews: Evidence from the Steam Store
在线评论剖析:来自 Steam 商店的证据
- 批准号:
2872725 - 财政年份:2023
- 资助金额:
$ 40万 - 项目类别:
Studentship